A View to a Kill: New Imaging Watches How Mitochondria Change During Disease

The most powerful machines are also the most destructive, a rule that applies even in the confines of the body’s cells. Mitochondria, the cell’s energy powerhouses, can fuel the development of many chronic and poorly understood conditions, including cancer, heart disease, and neuro­de­generative disorders such as Parkinson’s and Alzheimer’s. The disease process starts when environmental factors such as polluted drink­ing water or cigarette smoke perturb mitochondria, causing cellular levels of high-energy molecules called reactive oxygen species to spike.

Until now it has been unclear exactly how this destructive cascade unfolds. But researchers have developed an imaging technique that shows, in real time, what happens when things start going awry—a tool that could help doctors diagnose mitochondrial injuries before they have the chance to do serious cellular damage.

Scientists have long assumed that wounded mitochondria release reactive oxygen molecules, which then damage DNA and proteins, increasing disease risk. But some of the environmental chemicals that harm mitochondria produce these dangerous molecules themselves, prompting a “cause-and-effect question,” explains James M. Samet, a toxicologist at the National Health and Environmental Effects Research Laboratory in Chapel Hill, N.C., who has co-authored a study on the new technique in the journal Environmental Health Perspectives. Are these reactive molecules just injury by-products, or do they cause mitochondrial damage instead? “The only way you’re going to make heads or tails of this question is to actually observe, in real time, in living cells, these events as they unfold,” Samet says.

To do this, the researchers coaxed three fluorescent molecules into the mitochondria of living human skin cells. One lit up in the presence of hydrogen peroxide, a prominent reactive oxygen species, whereas the other two acted as mitochondrial injury sensors. Next they exposed the cells to a mitochondrial toxicant. The damage sensors lit up first, with the hydrogen peroxide marker following moments later, suggesting that the reactive oxygen molecules are indeed a sign, and not a cause, of injury.

Although more validation is necessary, Samet is confident that the development could help researchers understand the genesis of many chronic diseases.